From Bakery to Bench: How Scientists use Yeast for Biomedical Research

By Gaelyn Lyons

Yeast has been an essential tool to our society since the beginning of time. Beer, bread, and wine all use yeast due to their ability to undergo fermentation.1 Not only does yeast contribute to creating yummy food, but it also plays an important role in biomedical research. Many scientists, including some at Penn State College of Medicine, choose to use yeast in their studies due to the variety of advantages yeast provide.

What even is yeast? Yeast are eukaryotic fungi that can grow individually or in small clusters of cells (Figure 1).2 There are many species of yeast; most notable are Candida albicans, which is known to cause thrush and vaginitis (yeast infections), Cryptococcus neoformans, a pathogen that causes cryptococcosis in immunocompromised patients (like AIDS patients), and Saccharomyces cerevisiae, which is used in bread-baking.3 S. ceresivisea is also the predominant yeast used in biomedical research to investigate molecular and cellular processes that contribute to disease.

Figure 1: S. cerevisiae under a microscope. Kimball’s Biology Pages
 

There are many reasons why biomedical researchers utilize yeast like S. cerevisea. Yeast is cheap compared to other model organisms and can grow quickly.4 Similar to human cells, yeast are eukaryotic, meaning they contain a DNA-bound nucleus, and they undergo similar cell growth and division processes as mammalian cell models.2 In 1996, the yeast genome was fully defined, and soon after, yeast genes were discovered to be easily manipulated.4 Since then, many databases have been built to share information about yeast, including mutation collections, yeast-human homolog studies, and proteomic analyses.5 The sequencing of the yeast genome also led to the discovery of homologous proteins between yeast and human cells. A comparison study done in 1997 showed that 30% of known genes involved in human disease had a yeast ortholog.5 While this number may be smaller compared to other model organisms like Caenorhabditis elegans (60%) and mice (85%), yeast has a higher percentage of homologous genes compared to other non-mammalian single-cell models like Escherichia coli (9%). 6–8

Ever since the yeast genome was published, processes involved in human diseases have been studied in yeast.5 In 2001, Dr. Leland H. Hartwell was a pioneer in using yeast to study cancer genetics.9 Hartwell discoveredgenes that contribute to the development of cancer and was awarded the Nobel prize for his work in 2001.9 Yeast has also contributed to studying neurological diseases including Huntington’s, Parkinson’s, and Alzheimer’s disease by expressing proteins that are involved in the disease and investigating how the yeast cells are affected.5 Since 2001, there have been 11 Nobel prizes awarded for discoveries involving yeast research, and yeast continues to be used to investigate human diseases and advance biomedical techniques today.2 Many of these discoveries are being done closer to home than you may realize.

Multiple labs at Penn State College of Medicine use yeast in their research. One of which is that of the Biomedical Sciences Ph.D. Program director, Dr. Ralph Keil. Dr. Keil became interested in yeast research during his time in graduate school. Members of Dr. Jerry Fink’s laboratory presented their work in a seminar that Dr. Keil attended. After hearing about their work to identify transposons (genes that can move location in the genome) and develop a system to transform DNA into yeast (adding new genes to the yeast), Dr. Keil was hooked. He started researching yeast during graduate school, continued during his post-doc, and then brought his work to Penn State College of Medicine.

Dr. Keil’s lab investigated the genetic sequence HOT1 in yeast and found that it plays a role in promoting ribosomal DNA transcription. The Keil Lab also collaborated on a project to investigate the mechanism of volatile anesthetics. It is currently unknown how anesthesia works in humans, and the lab utilized yeast to determine the possible mechanism. “It’s a perfect use of yeast because you can do the genetics, and then you can identify what genes have mutations in them and understand the biology of what’s going on,” stated Dr. Keil. Their results identified that TORC1 pathway genes affect how the yeast responds to the volatile anesthetic isoflurane. “The big question that came back to haunt me with grants is ‘are you really learning anything about anesthesia in humans or dogs or cats or whatever?’ I can’t answer that, but we know what anesthetics do in yeast.”

When probed further about the use of yeast to study human disease, such as cancer, Dr. Keil replied, “You aren’t studying cancer. You’re studying DNA repair or control of replication. You’re learning the basic cellular processes, and then you’re able to build on that by asking, is this important in mammalian cells?”

Recently, Dr. Keil has been working with Dr. James Connor to clone human ferritin into yeast to create an iron supplement that is less stressful on the gastrointestinal (GI) tract and more bioavailable. Iron supplements have been reported to cause gastrointestinal issues like nausea, abdominal pain, and constipation and foods that contain iron have low bioavailablility.10,11 Creating an alternative iron-delivery method could allow for better absorption and minimize GI issues. These supplements would be similar to nutritional yeast, another food product that uses S. cerevisea.12 In the same way nutritional yeast is fortified with B vitamins and other minerals, yeast can be enriched with iron to provide better delivery.

So, the next time you take a bite out of your yeast rolls, don’t forget about all the amazing biomedical advances we’ve made because of a small fungus that can produce alcohol.

TL:DR

Yeast are eukaryotic cells that can be used for beer, bread, wine, and biomedical research.

Yeast have been used to study human diseases, including cancer and Alzheimer’s disease.

Many Penn State College of Medicine labs use yeast in their genetics research.


References

1.        Frazer, J. Yeast: Making Food Great for 5,000 Years. But What Exactly Is it? – Scientific American Blog Network. Scientific American (2013).

2.        Why Yeast is Important to Scientific Discovery. FenoLogica Biosciences https://www.fenologica.com/news/whyyeastisimportant (2017).

3.        Deacon, J. Yeasts: Saccharomyces, Cryptococcus, Candida. http://archive.bio.ed.ac.uk/jdeacon/microbes/yeast.htm.

4.        Duina, A. A., Miller, M. E. & Keeney, J. B. Budding Yeast for Budding Geneticists: A Primer on the Saccharomyces cerevisiae Model System. Genetics 197, 33 (2014).

5.        Mager, W. H. & Winderickx, J. Yeast as a model for medical and medicinal research. Trends Pharmacol. Sci. 26, 265–273 (2005).

6.        Why Mouse Matters. National Human Genome Research Institute https://www.genome.gov/10001345/importance-of-mouse-genome.

7.        Cecchetelli, A. & Morgan, L. Five Popular Model Organisms. Addgene https://blog.addgene.org/plasmids-101-five-popular-model-organisms.

8.        euGenes: Homologous Genes. http://eugenes.org/all/hgsummary.html.

9.        Pray, L. Yeast as a Model Organism for Studying Cancer | Learn Science at Scitable. Nat. Educ. 1, 183 (2008).

10.      Tolkien, Z., Stecher, L., Mander, A. P., Pereira, D. I. A. & Powell, J. J. Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis. PLoS One 10, (2015).

11.      Nowosad, K. & Sujka, M. The Use of Iron-Enriched Yeast for the Production of Flatbread. Mol. 2021, Vol. 26, Page 5204 26, 5204 (2021).

12.      Why Is Nutritional Yeast Good for You? https://www.healthline.com/nutrition/nutritional-yeast#TOC_TITLE_HDR_3.

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